Trial to Investigate the Safety and Efficacy of Cannabidiol Oral Solution (GWP42003-P; CBD-OS) in Children and Adolescents With Autism Spectrum Disorder

NCT04745026 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: GWND191892020-002819-21
• Study Type: interventional
• Target: 103
• Locations: 6 countries
• Sites: 23

Brief Summary

This study will be conducted to evaluate the efficacy of GWP42003-P, compared with placebo, in reducing symptom severity in children with Autism Spectrum Disorder (ASD).

Conditions

Autism Spectrum Disorder

Keywords

Cannabidiol oral solution; CBD-OS; GWP42003-P; Children; Adolescents

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in Aberrant Behavior Checklist (ABC) Subscale Total Scores

  The caregiver-assessed ABC was designed to assess the presence and severity of various problem behaviors commonly observed in individuals diagnosed with intellectual and developmental disability. The checklist contains 5 subscales: Irritability (15 items); Social Withdrawal (16 items); Stereotypic Behavior (7 items); Hyperactivity/Noncompliance (16 items); and Inappropriate Speech (4 items). Each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score of all items for each subscale range from 0-45 (irritability), 0-48 (social withdrawal and hyperactivity/noncompliance), 0-21 (stereotypic behavior), and 0-12 (inappropriate speech) where higher scores indicate worse clinical outcome. The change from baseline to Week 4, Week 8, and Week 12 is reported with lower scores indicating better clinical outcome.

  Baseline up to Week 12

• Change From Baseline in Vineland Adaptive Behavior Scales-3 (VABS-3) Scores

  The VABS-3 scales assess what a person does, rather than what he or she can do. The Vineland-3 assesses adaptive behavior in 3 domains: Communication, Daily Living Skills, and Socialization. Each domain is comprised of 3 subdomains: receptive expression and written (communication); personal, domestic and community (daily living skills); Interpersonal relationships, play and leisure and copying skills (socialization). The adaptive behavior composite score is calculated as arithmetic mean of all 3 domain scores. The total score range is 20 to 140, where low scores indicate low (worst) clinical outcome and high scores indicate high (best) clinical outcome. The change from baseline in VABS-3 is being reported with positive values indicating a positive improvement in adaptive behavior.

  Baseline up to Week 12

• Number of Patients Per Clinical Global Impression Improvement (CGI-I) Category

  The CGI-I is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. The clinician is asked: Compared to the patient's condition at admission to the project, how much has the patient changed? This is rated as: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; or 7 = very much worse. Higher scores indicate worse clinical outcome. The number of patients in each CGI-I category is reported.

  Day 85

• Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores

  The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's experience with patients who have the same diagnosis. The clinician is asked: Considering your total clinical experience with this particular population, how ill is the patient at this time? This is rated as: 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; or 7 = extremely ill. Higher scores indicate worse outcome. The change from baseline in CGI-S scores is reported and lower mean scores indicate better outcome.

  Baseline up to Week 12

Secondary Outcomes (10)

• Number of Participants Reporting Treatment-emergent Adverse Events

  Baseline up to Week 12

• Mean Change From Baseline in Hematology Clinical Laboratory Levels

  Baseline up to Week 9 (end of taper/withdrawal)

• Mean Percentage Change From Baseline in Hematology Clinical Laboratory Levels

  Baseline up to Week 9 (end of taper/withdrawal)

• Mean Change From Baseline in Hemoglobin Levels

  Week 9 (end of taper/withdrawal)

• Mean Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin Levels

  Week 9 (end of taper/withdrawal)

Study Arms (2)

GWP42003-P 10 mg/kg/day

EXPERIMENTAL

Participants will be stratified based on their age (6 to 11 years old, 12 to 17 years old), use of antipsychotics (on versus off), and region (North America versus Rest of the World) and will be randomized to receive 5 milligrams per kilogram per day (mg/kg/day) GWP42003-P for 1 week and then 10 mg/kg/day GWP42003-P for 11 weeks.

Drug: GWP42003-P

Placebo

PLACEBO COMPARATOR

Participants will be stratified based on their age (6 to 11 years old, 12 to 17 years old), use of antipsychotics (on versus off), and region (North America versus Rest of the World) and will be randomized to receive matching placebo for 12 weeks.

Drug: Placebo

Interventions

GWP42003-P DRUG

GWP42003-P oral solution (100 milligrams per milliliter \[mg/mL\] cannabidiol \[CBD\] in sesame oil with anhydrous ethanol, ethanol \[10% v/v\] sweetener \[sucralose\], and strawberry flavoring), administered twice a day (morning and evening)

Also known as: Epidiolex®, cannabidiol, CBD-OS

GWP42003-P 10 mg/kg/day

Placebo DRUG

Oral placebo to match GWP42003-P oral solution containing sesame oil with anhydrous ethanol, sweetener (sucralose), strawberry flavoring, and beta carotene, administered twice a day (morning and evening)

Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant weight is at least 12 kilograms (kg).
• Participants (if possessing adequate understanding, in the investigator's opinion) and their parent(s)/legal representative are willing and able to give informed assent and consent for participation in the trial.
• Participant and their caregiver are willing and able (in the investigator's opinion) to comply with all trial requirements.
• Participant has a diagnosis of Autism Spectrum Disorder (ASD) as per Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for ASD, confirmed by Autism Diagnostic Observational Schedule (ADOS-2) criteria (conducted within 2 years at the trial site or at screening by a qualified assessor). Note: During special circumstances (e.g., COVID-19 pandemic) where the ADOS-2 cannot be performed due to site restrictions (e.g., mandatory use of face masks) and an ADOS- 2 conducted within 2 years at the trial site by a qualified assessor is not available, eligibility can be confirmed using: 1) an ADOS-2 performed within 2 years by a qualified assessor (external to the site); 2) if 1) is not available, eligibility may be confirmed using the Autism Diagnostic Interview, Revised (ADI-R) at screening.
• Clinical Global Impressions - Improvement Scale (CGI-S) ≥ 4 (moderately ill) at screening and randomization.
• Intelligence quotient (IQ) ≥ 70 at screening, or measured within 1 year of screening, using Wechsler Abbreviated Scale of Intelligence Scale Second Edition (WASI-II).
• All medications or interventions (including psychosocial interventions, dietary supplements, probiotics, speech therapy, etc.) for ASD related symptoms must have been stable for 4 weeks prior to screening and randomization, and the patient/caregiver should be willing to maintain a stable regimen throughout the trial.
• Participants must have the ability to swallow the investigational medicinal product (IMP), provided as a liquid solution.
• Participant and/or parent(s)/legal representative is willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law.
• Participant and/or parent(s)/legal representative is/are willing to allow the participant's primary care practitioner (if they have one) and consultant (if they have one) to be notified of participation in the trial if the primary care practitioner/consultant is different from the investigator.

You may not qualify if:

• Current diagnosis of bipolar disorder, psychosis, schizophrenia, schizoaffective disorder, or major depression (participants with depression in remission may be included)
• Has a diagnosis other than ASD that dominates the clinical presentation (e.g., Attention Deficit Hyperactivity Disorder \[ADHD\])
• Has a progressive neurological condition
• Seizures in the past 24 weeks
• Changes in anticonvulsive therapy within the last 12 weeks
• Currently taking more than 2 anti-epileptic drugs (AEDs)
• Taking sirolimus, everolimus, temsirolimus, or tacrolimus
• Taking clobazam
• Taking omeprazole, lansoprazole, tolbutamide, or warfarin
• Taking repaglinide, pioglitazone, rosiglitazone, montelukast, bupropion, or efavirenz
• Currently using or has used recreational or medicinal cannabis, cannabinoid-based medications (including Sativex®, or Epidiolex®) within the 12 weeks prior to screening and is unwilling to abstain for the duration of the trial
• Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP, such as sesame oil.
• Participant has moderately impaired hepatic function at screening, defined as serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 × upper limit of normal (ULN) or total bilirubin (TBL) \> 2 × ULN. This criterion can only be confirmed once the laboratory results are available; participants enrolled into the trial who are later found to meet this criterion must be screen-failed.
• Participant is male and fertile (i.e., after puberty unless permanently sterile by bilateral orchidectomy) unless willing to ensure that they use male contraception (condom) or remain sexually abstinent during the trial and for 12 weeks thereafter.
• Participant is female and of childbearing potential (i.e., following menarche and until becoming postmenopausal for ≥ 12 consecutive months unless permanently sterile by hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) unless willing to ensure that they use a highly effective method of birth control (e.g., hormonal contraception, intrauterine device/hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence) during the trial and for 12 weeks thereafter.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (23)

Southwest Autism Research and Resource Center (SARRRC)

Phoenix, Arizona, 85006, United States

Location

UCSD School of Medicine

La Jolla, California, 92093, United States

Location

UCLA Neuropsychiatric Institute

Los Angeles, California, 90024, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

APG Research, LLC

Orlando, Florida, 32803, United States

Location

University of Louisville

Louisville, Kentucky, 40292, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital (Lurie Center for Autism)

Lexington, Massachusetts, 02421, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Red Oak Psychiatry Associates, PA

Houston, Texas, 77090, United States

Location

Seattle Children's Research Institute

Seattle, Washington, 98105, United States

Location

Monash Medical Centre

Clayton, 03168, Australia

Location

Queensland Children's Hospital

South Brisbane, 4101, Australia

Location

The Kids Clinic

Ajax, Ontario, L1Z0M1, Canada

Location

Center for Pediatric Excellence

Ottawa, Ontario, K2G1W2, Canada

Location

Klinik fur Psychiatrie, Psychotherapie und Psychosomatik im Kindes und Jugendalter

Freiburg im Breisgau, 79104, Germany

Location

Zentralinstitut fuer Seelische Gesundheit

Mannheim, 68159, Germany

Location

Instituto Global de Atencion Integral del Neurodesarrollo (IGAIN)

Barcelona, 08007, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Corporacio Sanitaria Parc Tauli

Sabadell, 08208, Spain

Location

University of Glasgow Institute of Health and Wellbeing

Glasgow, G128QQ, United Kingdom

Location

Institute of Psychiatry, King's College London

London, United Kingdom

Location

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Clinical Trial Disclosure & Transparency
• Organization: Jazz Pharmaceuticals

ClinicalTrialDisclosure@JazzPharma.com

215-832-3750

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2021
• First Posted: February 9, 2021
• Study Start: May 31, 2021
• Primary Completion: December 21, 2023
• Study Completion: December 21, 2023
• Last Updated: March 30, 2025
• Results First Posted: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); DE (2); CA (2); ES (3); US (12); AU (2)